【摘要】 目的:观察N-正丁基氟哌啶醇碘化物（F₂）对大鼠心肌缺血再灌注损伤及大鼠心室肌细胞L-型钙电流(I_Ca)的影响。方法:大鼠冠脉左前降支结扎30 min后恢复灌注30 min,于缺血前分别静脉注射F₂（1,2,和4 mg/kg）。测定血浆CK、CK-MB、LDH、HBDH、GOT、MDA的含量及SOD活性;观察心肌的形态学改变。采用酶急性分离的大鼠单个心室肌细胞,应用膜片箝全细胞记录技术,观察F₂对I_Ca的影响。结果:F₂呈量效依赖地降低缺血再灌注心肌酶CK、CK-MB、LDH、HBDH、GOT的释放,保护SOD的活性,降低MDA的产生;电镜下可见F₂减轻心肌的形态学改变。F₂ 1 μmol/L明显抑制I_Ca,使峰电流从（1775±360）pA减少至（464±129）pA（n=8,P<0.01）,并使得I_Ca的I-V曲线上移,但不改变其电压依赖特征。结论:F₂对大鼠心肌缺血再灌注损伤具有拮抗作用,并可抑制大鼠心室肌细胞L-型钙电流。F₂对心肌缺血再灌注损伤的拮抗作用及其扩张血管的机制可能与其阻断L-型钙通道有关。更多还原

【Abstract】 AIM: To study the effects of N-n-butyl haloperidol iodide （F₂） on rat heart ischemia/reperfusion （I/R） injury and L-type calcium current (I_Ca) in rat ventricular myocytes. METHODS: Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring perfusion for 30 min. F₂ （1, 2, and 4 mg/kg） were iv injected before ischemia. Plasma creatine kinase （CK）, creatine kinase isoenzyme MB （CK-MB）, lactate dehydrogenase （LDH）, α-hydroxybutyrate dehydrogenase （HBDH）, glutamic-oxaloacetic transaminase （GOT）, malondialdehyde （MDA） concentrations, and superoxide dismutase （SOD） activity were measured. The pathologic changes of I/R myocardium were assessed by the transmission electron microscopy. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique. RESULTS: F₂ reduced the release of CK, CK-MB, LDH, HBDH and GOT, preserved the activity of SOD, and decreased the MDA contents dose-dependently. For morphology, F₂ mollified the pathologic changes of myocardium induced by I/R injury. F₂ 1 μmol/L decreased I_Ca from （1775±360） pA to （464±129） pA （n=8, P<0.01） and shifted the current-voltage of I_Ca upward, without affecting the voltage-dependent properties of I_Ca. CONCLUSION: F₂ played a protective role against rat heart I/R injury in a dose-dependent manner, and inhibited I_Ca in rat ventricular myocytes. The cardioprotective and vasodilatory mechanisms of F₂ may be related to its inhibitory effect on L-type calcium channel.更多还原